Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
1. The Applicant’s response to the office action filed on July 22, 2025 is acknowledged.
Status of the Application
2. Claims 53 and 56-74 are pending under examination. New claim 75 is added. Claims 1-52, 60-61 were canceled. The Applicant’s arguments and the amendment have been fully considered and found unpersuasive for the following reasons.
Maintained Claim Rejections - 35 USC § 103
3. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 53 and 56-75 are rejected under 35 U.S.C. 103 as being unpatentable Fan et al. (US 2018 /0088112) in view of Shannon et al. (US 2008/0032310).
Note regarding claim 75 reciting product by process, the claim 75 is interpreted as a product as noted in MPEP 2113-I.
Fan et al. teach a kit of claim 53, 75, comprising (a) an array comprising a plurality of capture probes affixed to the array, wherein in a capture probe of plurality of capture probes comprises a capture domain and a spatial barcode (para 0010, 0012-0019, 0045-0046-0052, 0057-0059);
(b) a first analyte-binding moiety (first protein binding reagent) conjugated to a first oligonucleotide comprising a first barcode; and a second analyte binding moiety conjugated to a second oligonucleotide comprising a second barcode (para 0006-0007, 0009-0010, 0020-0024, 0053-0056, 0185-0192);
(c) a third oligonucleotide (splint oligonucleotide), wherein the third oligonucleotide comprises a sequence that is substantially complementary to the first oligonucleotide and substantially complementary to the second oligonucleotide (para 0165-0168 0185-0192, 0159, 0606);
With reference to claims 56-57, Fan et al. teach that the first oligonucleotide further comprises a first functional sequence, or a first unique molecular identifier (UMI) and second oligonucleotide comprises a second functional sequence, or a second unique molecular identifier (UMI) (para 0006, 0009-0010, 0310, 0343);
With reference to claims 58-59, 73, Fan et al. teach that the first oligonucleotide comprises one or more uracil nucleotides and the second oligonucleotide comprises a capture domain and one or more uracil nucleotides and the polymerase is U (+) or U (-) polymerase (para 0294, 0043, 0059, 0198).
With reference to claims 60-61, Fan et al. teach that the first analyte-binding moiety is a first protein which is a first antibody comprising antigen-binding fragment and the second analyte-binding moiety is a second protein which is a second antibody comprising antigen-binding fragment or peptide ligand (para 0280-0281, 0475-0476, 0033).
With reference to claim 62-63, Fan et al. teach that the first analyte-binding moiety or the second analyte-binding moiety is associated with a linker comprising photocleavable linker and the first or second oligonucleotide comprises a free 3’-end (para 0006, 0536-0538, 0349, 0053, 0168, 0016, 0049).
With regard to claims 64-65, Fan et al. teach that the first and the second barcode are same or different (para 0527, 0006, 0192, 0521).
With regard to claim 66, Fan et al. the third oligonucleotide comprises a sequence of about 20 to 60 nucleotides (para 0162, 0185-0186, 0085).
With regard to claims 67-71, Fan et al. teach that the first and second proteins are selected from a cell surface moiety and the host protein, viral protein antibodies, antigen binding fragments (para 0281, 0341).
With regard to claims 72, Fan et al. teach that the first oligonucleotide further comprises a first bridge sequence and the second oligonucleotide further comprises a second bridge sequence, wherein the first and second bridge sequences are substantially complementary to each other (para 0030, 0036).
With reference to claim 74, Fan et al. teach that the second oligonucleotide further comprises a capture probe domain sequence that is complementary to the capture domain of the capture probe affixed to the array (para 0106, 0192, 0126, 0147, 0174).
Although Fan et al. teach proximity ligation, however, Fan et al. did not specifically teach kit comprising a ligase and third oligonucleotide comprising blocking probe hybridized to the capture probe capture domain.
Shannon et al. teach a kit comprising proximity probes and a splint oligonucleotide comprising blocked oligonucleotide sequence and a ligase, wherein Shannon et al. teach a probe set ligation using a splint oligonucleotide that is modified to block the unwanted primer extension and reduces accumulation of ligated products (para 0176-0177, 0192-0193, 0199).
It would have been prima facie obvious to an ordinary person skilled before the effective filing date of the invention to combine the kit comprising proximity probes as taught by Fan et al. with the kit comprising a ligase and blocked splint oligonucleotide as taught by Shannon et al. to develop a ready to use composition for sensitive detecting multiple protein targets. The ordinary person skilled in the art would have been motivated to modify the kit comprising the proximity probes, blocked splint oligonucleotide and a ligase as taught by Shannon et al., and have a reasonable expectation of success because both references teach proximity probes and a third (bridge or splint) oligonucleotide, wherein Shannon et al. explicitly taught kit comprising a blocked splint oligonucleotide and a ligase, wherein the blocked splint oligonucleotide prevents unwanted primer extension and reduces the accumulation of ligation products (para 0176-0177, 0192-0193, 0199) and such a modification of the kit composition is considered obvious over the cited prior art.
Response to Arguments:
With reference to the rejection of claims 53 and 56-74 under 35 USC 103, the Applicant’s arguments and the amendment have been fully considered. However, the combination of the Fan et al. and Shannon et al. teach the limitations as amended and the rejection is maintained and restated to address the amendment.
Conclusion
No claims are allowable.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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Suryaprabha Chunduru
Primary Examiner
Art Unit 1681
/SURYAPRABHA CHUNDURU/Primary Examiner, Art Unit 1681